The DOI matches its Crossref record; 75 of the 78 references it cites were found in a registry or an index.
Synaptic Activity Reduces Intraneuronal Aβ, Promotes APP Transport to Synapses, and Protects against Aβ-Related Synaptic Alterations
Open accessAbstract
A central question in Alzheimer's disease research is what role synaptic activity plays in the disease process. Synaptic activity has been shown to induce β-amyloid peptide release into the extracellular space, and extracellular β-amyloid has been shown to be toxic to synapses. We now provide evidence that the well established synaptotoxicity of extracellular β-amyloid requires γ-secretase processing of amyloid precursor protein. Recent evidence supports an important role for intraneuronal β-amyloid in the pathogenesis of Alzheimer's disease. We show that synaptic activity reduces intraneuronal β-amyloid and protects against β-amyloid-related synaptic alterations. We demonstrate that synaptic activity promotes the transport of the amyloid precursor protein to synapses using live cell imaging, and that the protease neprilysin is involved in reduction of intraneuronal β-amyloid with synaptic activity.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Recently, additional evidence pointed to the importance of amyloidogenic processing of APP, and therefore potentially intraneuronal Aβ, in extracellular Aβ-induced synapse dysfunction [190].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [190]
In the citing paper
“In fact synaptic activity was recently shown to promote APP transport down neurites to synapses [190].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [190]
In the citing paper
“Moreover, synaptic activity was recently shown to reduce the intraneuronal pool of Aβ in vitro and in vivo [190].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [190]
In the citing paper
“A recent neurobiological study showed that it was reduction of intraneuronal rather than extracellular Aβ that correlated with synaptic improvement [190].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [190]
In the citing paper
“Work in the 1990s had shown that extracellular Aβ1-42 led to marked up-regulation of endogenously generated Aβ42 [51, 211], which also occurs in neurons [190].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [190]
In the citing paper
“The protease shown to most efficiently degrade Aβ, neprilysin [81], was reported to be critical in synaptic activity-induced intraneuronal Aβ42 reduction [190].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [190]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744
Alzheimer's Disease Is a Synaptic Failure
Selkoe, D. J. (2002) · Science · doi:10.1126/science.1074069 · Cited by 4,420
Terry, R. D., Masliah, E., Salmon, D. P., Butters, N., DeTeresa, R., Hill, R., Hansen, L. A., & Katzman, R. (1991) · Annals of Neurology · doi:10.1002/ana.410300410 · Cited by 4,397
Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., & Cole, G. (1996) · Science · doi:10.1126/science.274.5284.99 · Cited by 4,210
Triple-Transgenic Model of Alzheimer’s Disease with Plaques and Tangles
Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., & LaFerla, F. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00434-3 · Cited by 4,126
Shankar, G. M., Li, S., Mehta, T. H., Garcia-Munoz, A., Shepardson, N. E., Smith, I., Brett, F. M., Farrell, M. A., Rowan, M. J., Lemere, C. A., et al. (2008) · Nature Medicine · doi:10.1038/nm1782 · Cited by 3,685
Synapse loss in frontal cortex biopsies in Alzheimer's disease: Correlation with cognitive severity
DeKosky, S. T., & Scheff, S. W. (1990) · Annals of Neurology · doi:10.1002/ana.410270502 · Cited by 2,376
Intracellular amyloid-β in Alzheimer's disease
LaFerla, F. M., Green, K. N., & Oddo, S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2168 · Cited by 1,942
Palop, J. J., Chin, J., Roberson, E. D., Wang, J., Thwin, M. T., Bien-Ly, N., Yoo, J., Ho, K. O., Yu, G.-Q., Kreitzer, A., et al. (2007) · Neuron · doi:10.1016/j.neuron.2007.07.025 · Cited by 1,653
APP Processing and Synaptic Function
Kamenetz, F., Tomita, T., Hsieh, H., Seabrook, G., Borchelt, D., Iwatsubo, T., Sisodia, S., & Malinow, R. (2003) · Neuron · doi:10.1016/s0896-6273(03)00124-7 · Cited by 1,644
Research works printed but not linked: 1
- 10.1097/00002093-200607001-00010 · DOI · Paper page
Cited by
Sorted by citations
Items 101–127 of 127
Aow, J., Huang, T.-R., Goh, Y. T., Sun, A. X., Thinakaran, G., & Koo, E. H. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112774 · Cited by 12
Godoy, P. A., Mennickent, D., Cuchillo‐Ibáñez, I., Ramírez-Molina, O., Silva-Grecchi, T., Panes-Fernández, J., Castro, P. A., Sáez‐Valero, J., & Fuentealba, J. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111968 · Cited by 8
Anglada‐Huguet, M., Endepols, H., Sydow, A., Hilgers, R., Neumaier, B., Drzezga, A. E., Kaniyappan, S., Mandelkow�, E., & Mandelkow, E.-M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24119260 · Cited by 7
Garcia, M. G., Paulus, A., Vázquez‐Reyes, S., Klementieva, O. L., Gouras, G. K., Bachiller, S., & Deierborg, T. (2023) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2023.100663 · Cited by 5
Self-citationsAPPα Inhibits Neurite Outgrowth in Primary Mouse Neurons via GABA B Receptor Subunit 1a
Barber, D., Salinas-Salinas, C., Houmam, S., Shukla, K., & Rice, H. C. (2026) · eNeuro · doi:10.1523/eneuro.0345-25.2026 · Cited by 4
Analysis of Vesicular Trafficking in Primary Neurons by Live Imaging
Tampellini, D., & Gouras, G. K. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-328-8_22 · Cited by 4
Self-citationThe mevalonate suppressor δ-tocotrienol increases AMPA receptor-mediated neurotransmission
Wei, W., Yount, S. T., Allen, Z. D., Bechdol, K., Xia, W., Mo, H., & Mabb, A. M. (2022) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2022.11.052 · Cited by 3
Ren, Q., Wang, S., Li, J., Cao, K., Zhuang, M., Wu, M., Geng, J., Jia, Z., Xie, W., & Liu, A. (2024) · Journal of Neuroscience · doi:10.1523/jneurosci.1689-23.2024 · Cited by 3
Bengtsson, S. K. S. (2013) · DiVA at Umeå University (Umeå University) · Cited by 3
Induced neuronal activity does not attenuate amyloid beta‐induced synaptic loss in vitro
Kono, R., Kim, G. L., Nagata, H., Ikegaya, Y., & Koyama, R. (2019) · Neuropsychopharmacology Reports · doi:10.1002/npr2.12074 · Cited by 2
γ-secretase inhibitors for treating Alzheimer’s disease: rationale and clinical data
Panza, F., Frisardi, V., Imbimbo, B. P., Seripa, D., Solfrizzi, V., & Pilotto, A. (2011) · Clinical Investigation · doi:10.4155/cli.11.86 · Cited by 2
Origin(s) of Intraneuronal Amyloid
D’Andrea, M. R. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-804256-4.00002-4 · Cited by 2
Beneficial Effects of Citrus Flavonoids Against Aβ Pathology in Alzheimer’s Disease
Javed, H., Ojha, S. K., & Jamali, M. C. (2022) · Springer eBooks · doi:10.1007/978-981-16-7606-2_19 · Cited by 1
Lin, M. (2010)
Self-citationPathological Consequences of Aβ From Extracellular to Intraneuronal
D’Andrea, M. R. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-804256-4.00004-8
Lundgren, J. L. (2018) · Figshare
Amyloid beta: from pre-analytical factors to disease mechanisms
Toombs, J. (2019) · UCL Discovery (University College London)
The effect of irrelevant visual experience on visual memory
Indulkar, S. S. (2019) · KU ScholarWorks (The University of Kansas)
Small Molecular Weight Compounds Antagonistic to Amyloid Peptide25-35
Williams, W. R. (2021) · Journal of Biosciences and Medicines · doi:10.4236/jbm.2021.91004
Amyloid precursor protein and axonal transport
Rodrigues, E. M. (2010) · eScholarship (California Digital Library)
Physiological and pathological roles of the amyloid precursor protein at the presynapse
Jordá-Siquier, T. (2021) · theses.fr (ABES) · doi:10.70675/3bff9a77z3935z4d28zb02bz5b454bcbc77e
Lam, S. (2021) · theses.fr (ABES) · doi:10.70675/60b353ffz56fcz41a2z9e53zf0d9ac078167 · Cited by 1
Role of T-cell immunity in the pathophysiology of Alzheimer’s disease and other Tauopathies
Matta, K. (2024) · theses.fr (ABES) · doi:10.70675/cea4fe5ez67c3z4445z92f7z39af62ba059b
Yu, X., Ren, Q., Gao, Y., Xie, S., Dang, R., Meng, J., Su, Z., Li, M., Ao, Y., Liu, A., et al. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.118063
Metadata
- Authors
- Tampellini, D., Rahman, N., Gallo, E. F., Huang, Z., Dumont, M., Capetillo-Zarate, E., Ma, T., Zheng, R., Lu, B., Nanus, D. M., Lin, M. T., & Gouras, G. K.
- Affiliations
- Cornell University (US)
- Weill Cornell Medicine (US)
- Harvard University (US)
- Rockefeller University (US)
- Corresponding author
- Gouras, Gunnar K.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-08-05
- Volume
- 29
- Issue
- 31
- Pages
- 9704-9713
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2763626
- OpenAlex
- W2094929105
- Cited by
- 127
- References
- 78
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 4 · 2022: 5 · 2021: 9 · 2020: 4 · 2019: 8 · 2018: 6 · 2017: 7 · 2016: 8 · 2015: 6 · 2014: 8 · 2013: 12 · 2012: 11
- FWCI
- 10.16
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Alzheimer's Association (AG09464)
- Weill Cornell Medical College
- National Institute on Aging (R01AG027140, AG09464, R01AG020729, K02AG028174, AG 20729, AG028174, AG027140, P01AG009464)
- National Institute of Neurological Disorders and Stroke (R01NS045677)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- synaptic activity, synaptotoxicity, neprilysin, Alzheimer's disease, synaptic plasticity, live-cell imaging
- MeSH terms
- Disks Large Homolog 4 Protein, Animals, Biological Transport, Active, Cells, Cultured, Extracellular Space, Hippocampus, Humans, Interneurons, Membrane Proteins, Mice, Transgenic, Synaptic Transmission, Neuronal Plasticity, Peptide Fragments, Receptors, Cell Surface, Synapses, Neprilysin, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Long-Term Potentiation, Intracellular Signaling Peptides and Proteins, Mice, Guanylate Kinases, Amyloid Precursor Protein Secretases, Protease Nexins, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
